High-dose-rate Rotte "Y" applicator brachytherapy for definitive treatment of medically inoperable endometrial cancer: 10-year results

PURPOSE: To assess the intermediate clinical outcomes of medically inoperable patients with endometrial cancer treated with definitive Rotte "Y" applicator high-dose-rate brachytherapy (HDRB) over a 10-year period. METHODS AND MATERIALS: Forty-nine inoperable patients were treated with HDRB from 1997 to 2007. Forty three (84%) were markedly obese (body mass index >35 kg/m(2)). Thirty-one patients (63.3%) underwent two-dimensional treatment planning, whereas 18 patients (36.7%) underwent three-dimensional treatment planning. Thirty five of the patients (71.4%) were first treated with external beam radiotherapy (EBRT). For patients receiving EBRT in addition to HDRB, the median Y-applicator dose was 20 Gy in 5 fractions; for patients receiving HDRB alone it was 35 Gy in 5 fractions. All patients received two Y-applicator treatments per day. RESULTS: Median follow-up time for all patients was 33 months. Acute HDRB toxicities were limited to Grade 1 and 2 occurring in 5 patients. One patient had a myocardial infarction. Four patients had late Grade 2 or 3 toxicity. Three patients had local recurrence (median time to recurrence, 16 months). The 3- and 5-year actuarial cause-specific survival rates were 93% and 87%, respectively; the overall survival rate was 83% and 42%, respectively, at 3 and 5 years. CONCLUSIONS: Twice-daily HDRB using a Y-applicator is a well-tolerated and efficacious regimen for the definitive treatment of medically inoperable patients with early-stage endometrial cancer. The recent incorporation of three-dimensional treatment planning has the potential to further decrease treatment morbidities.     

Figo IIIB squamous cell carcinoma of the cervix: an analysis of prognostic factors emphasizing the balance between external beam and intracavitary radiation therapy

PURPOSE: To define patient, tumor, and treatment factors that influence the outcome of patients with FIGO Stage IIIB squamous cell carcinoma of the intact uterine cervix. METHODS AND MATERIALS: The records of 1,096 patients treated with radiation therapy between 1960 and 1993 for FIGO Stage IIIB squamous cell carcinoma of the intact uterine cervix were reviewed retrospectively. Of these, 983 (90%) were treated with curative intent and 113 were treated only to achieve palliation of symptoms. Of 907 patients who completed the intended curative treatment, 641 (71%) were treated with a combination of external beam irradiation (EBRT) and intracavitary irradiation (ICRT) and 266 (29%) were treated with EBRT only. The median duration of treatment for these 907 patients was 51 days. Between 1966 and 1980, only 52% of patients who completed treatment with curative intent received ICRT, compared with 92% of patients treated during 1981-1993, an increase that reflects an evolution in the philosophy of treatment for advanced tumors. In general, the intensity of ICRT correlated inversely with the dose of EBRT to the,central pelvis. Median follow-up of surviving patients was 134 months. RESULTS: For 983 patients treated with initial curative intent, disease-specific survival (DSS) was significantly worse for those who were < 40 years old, had experienced more than a 10% weight loss, or had a hemoglobin level < 10 g/dl before or during radiation therapy. Tumor factors that correlated with a relatively poor DSS were bilateral pelvic wall involvement, clinical tumor diameter > or = 8 cm, hydronephrosis, lower vaginal involvement, and evidence of lymph node metastases on lymphangiogram (p < 0.01 in all cases). For the 907 patients who completed treatment with curative intent, 641 who had ICRT had a DSS of 45% at 5 years, compared with 24% for those treated with EBRT alone (p < 0.0001). Those who received > 52 Gy of EBRT to the central pelvis had DSS rates of 27-34%, compared with 53% for patients treated with lower doses of EBRT to the central pelvis and more intensive ICRT (p < 0.0001). At 5 years, the actuarial risk of major complications was also greater for patients treated with > 52 Gy of EBRT to the central pelvis (57-68%), compared with those who had 48-52 Gy (28%) and those who had < or = 47 Gy of EBRT to the central pelvis (15%) (p < 0.0001). Outcome was also compared for four time periods during which different treatment policies were in place for patients with Stage IIIB disease. The highest DSS (51%) and lowest actuarial complication rate (17%) were achieved during the most recent period (1981-1993) when modest doses of EBRT were combined with relatively intensive ICRT (p < 0.01 for both comparisons). CONCLUSION: Aggressive use of ICRT, carefully balanced with pelvic EBRT, is necessary to achieve the best ratio between tumor control and complications for patients with FIGO Stage IIIB carcinoma of the cervix. In our experience, the highest DSS rates and the lowest complication rates were achieved with a combination of 40-45 Gy of EBRT combined with ICRT.     

Is there a role for a brachytherapy vaginal cuff boost in the adjuvant management of patients with uterine-confined endometrial cancer?

Purpose/Objective: Many patients who have uterine-confined endometrial cancer with prognostic factors predictive of recurrence are treated with adjuvant pelvic radiation. The addition of a brachytherapy vaginal cuff boost is controversial.Materials and Methods: Between 1983 and 1993, 270 patients received adjuvant postoperative pelvic irradiation following hysterectomy for Stage I or II endometrial cancer. Group A includes 173 patients who received external beam irradiation alone (EBRT), while group B includes 97 patients who received EBRT with a vaginal brachytherapy application. The median dose of EBRT was 45 Gy. Vaginal brachytherapy consisted of a low dose rate ovoid or cylinder in 41 patients, a high dose rate cylinder in 54 patients, and a radioactive gold seed implant in two patients. The median follow-up time was 64 months. The two groups were compared in terms of age, histologic grade, favorable versus unfavorable histology, capillary space invasion, depth of myometrial invasion, and pathologic stage.Results: Chi-square analysis revealed that the only difference between the two groups was the presence of more Stage II patients in group B (38% versus 14%). No difference was detected for 5 year pelvic control and disease-free survival rates between groups A and B.Conclusion: There is no suggestion that the addition of a vaginal cuff brachytherapy boost to pelvic radiation is beneficial for pelvic control or disease-free survival for patients with Stage I or II endometrial cancer. Prospective randomized trials designed to study external irradiation alone versus external beam treatment plus vaginal brachytherapy are unlikely to show a positive result. Because EBRT provides excellent pelvic control, protocol development for uterine-confined corpus cancer should focus on identifying patients at risk for recurrence as well as other means of augmenting EBRT (e.g. addition of chemotherapy) in order to improve disease free survival in those subgroups.     

Long-term results of high-dose rate intracavitary brachytherapy for squamous cell carcinoma of the uterine cervix

BACKGROUND: The authors performed a long-term follow-up study to evaluate the efficacy and late toxicity of high-dose rate intracavitary brachytherapy (HDR-ICBT) for cervical carcinoma. METHODS: From 1968 to 1986, 1148 patients with Stage IB to IVB squamous cell carcinoma of the cervix (staging was performed according to the International Federation of Gynecology and Obstetrics) were treated with a combination of external beam radiotherapy (EBRT) and HDR-ICBT. For patients with early-stage disease, 20 gray (Gy) of EBRT was delivered to the whole pelvis, followed by 24 Gy/4 fractions of HDR-ICBT and 30 Gy of central-shielding EBRT. For patients with advanced-stage disease, 20-40 Gy of whole pelvic EBRT was administered, followed by 24 Gy/4 fractions of ICBT and 30-10 Gy of central-shielding EBRT. The overall treatment time was approximately 6 weeks. Among survivors, the follow-up rate was 98% and the median follow-up duration was 22 years. RESULTS: The 10-year pelvic tumor control rates were 93% for patients with Stage IB disease, 82% for patients with Stage II disease, and 75% for patients with Stage III disease. The 10-year overall and cause-specific survival rates were 74% and 89% for patients with Stage IB disease, 52% and 74% for patients with Stage II disease, and 42% and 59% for patients with Stage III disease, respectively. The 10-year actuarial rates of major complications were 4.4% in the rectosigmoid colon, 0.9% in the bladder, and 3.3% in the small intestines. CONCLUSIONS: The results of the current study suggest that the combination of EBRT and HDR-ICBT according to the authors' protocol provided outcomes that were comparable to those of the conventional low-dose rate brachytherapy with acceptable rates of late complications in the treatment of cervical carcinoma.     

Definitive radiotherapy for patients with isolated vaginal recurrence of endometrial carcinoma after hysterectomy

PURPOSE: To determine the outcome of patients after radical radiotherapy (RT) for isolated vaginal recurrence of endometrial carcinoma and to determine the clinical and pathologic predictors of outcome. METHODS AND MATERIALS: We reviewed the records of 91 patients treated at our institution between 1960 and 1997 with radical RT for vaginal recurrence after definitive surgery for endometrial carcinoma. Thirty-one percent of the patients received external beam RT (EBRT) alone, 12% received brachytherapy alone, and 57% received a combination. The median dose of radiation was 75 Gy (range 34-122). All end points were measured from the time of the first recurrence. The median duration of follow-up after recurrence was 58 months (range 1-289). RESULTS: The 2- and 5-year local control (LC) rate and overall survival rate was 82% and 75% and 69% and 43%, respectively. The median time from initial diagnosis of endometrial cancer to death from disease was 38 months. On univariate analysis, a dose to the relapse site of > or =80 Gy and EBRT plus brachytherapy vs. single-modality therapy were significant predictors of improved LC. On multivariate analysis, only the type of treatment correlated significantly with LC (p = 0.03). On univariate analysis, Grade 1 or 2 vs. Grade 3 tumor and EBRT plus brachytherapy vs. single-modality therapy were significant predictors of improved overall survival. CONCLUSION: RT provides excellent LC of isolated vaginal recurrences of endometrial carcinoma, particularly when high doses are given using a combination of EBRT and brachytherapy. However, distant metastases frequently develop despite local disease control, contributing to a 5-year overall survival rate of <50%. For patients who have an isolated vaginal recurrence, the time from initial diagnosis of endometrial cancer to death from disease is usually >3 years. For this reason, in studies of adjuvant RT, long-term follow-up is required to permit evaluation of the impact of treatment on survival.     

Long-term outcomes after external beam irradiation and brachytherapy boost for base-of-tongue cancers

PURPOSE: To assess long-term efficacy and toxicity associated with external beam irradiation (EBRT) and interstitial (192)Ir implantation for the treatment of squamous carcinoma of the base of tongue. METHODS AND MATERIALS: Between April 1975 and December 1993, 41 patients with base-of-tongue carcinomas were treated with (192)Ir interstitial implants after EBRT at Stanford University. One patient had Stage I, 6 had Stage II, 7 had Stage III, and 27 had Stage IV tumors. Twenty-eight patients had cervical lymph node involvement at diagnosis. All received EBRT to a median dose of 50 Gy (range 48.9-68 Gy) to the primary tumor and regional lymph nodes before brachytherapy. Interstitial implant was performed 2-4 weeks after EBRT. Intraoperatively, nylon catheters were placed via steel trocars into the base of tongue, glossotonsillar groove, and pharyngo-epiglottic fold using a catheter looping technique. Twenty-three of 28 node-positive patients also underwent simultaneous neck dissections. Postoperatively, the (192)Ir seeds were inserted and allowed to remain in place for approximately 35 h to achieve a median tumor dose of 26 Gy (range 20-34 Gy) to a median volume of 73 cc. Survival, local control, and complications were assessed. RESULTS: With a median follow-up of 62 months (range 9-215) for all patients and 90 months for alive patients, the 5-year Kaplan-Meier survival estimate was 66%. The 5-year local control rate was 82%, with 7 patients recurring locally, 2 of whom were salvaged with surgery. Nodal control was achieved in 93% of patients with either EBRT alone or in combination with neck dissection. The 5-year freedom from distant metastasis rate was 83%. Acute complications included transient bleeding (5%) and infection (8%). Late complication included soft-tissue necrosis/ulceration (7%), osteoradionecrosis (5%), and xerostomia. CONCLUSION: Base-of-tongue carcinoma can be effectively treated with EBRT and (192)Ir implant boost. Local control is excellent and complication rates are acceptable.     

Radiation therapy in the treatment of endometrial stromal sarcoma

OBJECTIVE: The efficacy of radiation therapy in the treatment of endometrial stromal sarcoma (ESS) is still not clear. We report our results over an 18-year period in comparison to data from literature concerning adjuvant radiation therapy and other treatment modalities. PATIENTS AND METHODS: During 1981-1998, 21 patients with ESS were treated at General Hospital Vienna. The age of the patients ranged between 44-76 years (median: 65 yr). The 1989 FIGO classification for endometrial carcinoma was used in this study retrospectively. Eleven patients presented in Stage I, 1 in Stage II and 5 in Stage III. Four patients had Stage IV tumors or recurrences. The majority of patients (66.7%) had a Grade 3 tumor. Seventeen patients were treated in a curative intent. Fifteen patients were referred for postoperative radiotherapy after hysterectomy. Thirteen of them received a combined radiotherapy. Two patients were referred for primary radiotherapy. They received a combined radiotherapy. Four patients were referred for radiotherapy with a palliative intent. Twenty patients received external beam therapy (EBT) in daily fractions of 1.6-2.0 Gy up to a total dose of 27-57 Gy to the pelvis. Seventeen patients received brachytherapy. RESULTS: Follow-up was 8 to 170 months (mean: 70.3 months, median: 64 months). Eleven patients are still alive, 10 without tumor and 1 with tumor. Ten patients are dead, 6 due to ESS, 1 due to breast cancer, and 3 due to intercurrent diseases. After adjuvant radiotherapy, 3 patients had tumor recurrences. All had distant metastases, and 1 had local failure additionally. Two patients with primary treatment died due to intercurrent disease without tumor. The overall actuarial survival and the disease-specific survival rates were 63.4% and 80.9% after 5 years and 52.8% and 80.9% after 10 years. The overall local control rate was 93.8% after 5 years. Four patients treated with a palliative intent showed partial response. Three patients died rapidly due to tumor. One patient with a Grade 1 tumor is still alive 12 months after treatment. CONCLUSION: In our experience, surgery and adjuvant radiation therapy are most effective treatments for patients with ESS due to the excellent local control in all stages and the good disease-specific survival in early stages.     

Adjuvant brachytherapy removes survival disadvantage of local disease extension in stage IIIC endometrial cancer: a SEER registry analysis

PURPOSE: To assess the role of radiotherapy (RT) in women with Stage IIIC endometrial cancer. METHODS AND MATERIALS: The 17-registry Survival, Epidemiology, and End Results (SEER) database was searched for patients with lymph node-positive non-Stage IV epithelial endometrial cancer diagnosed and treated between 1988 and 1998. Two subgroups were identified: those with organ-confined Stage IIIC endometrial cancer and those with Stage IIIC endometrial cancer with direct extension of the primary tumor. RT was coded as external beam RT (EBRT) or brachytherapy (BT). Observed survival (OS) was reported with a minimum of 5 years of follow-up; the survival curves were compared using the log-rank test. RESULTS: The therapy data revealed 611 women with Stage IIIC endometrial cancer during this period. Of these women, 51% were treated with adjuvant EBRT, 21% with EBRT and BT, and 28% with no additional RT (NAT). Of the 611 patients, 293 had organ-confined Stage IIIC endometrial cancer and 318 patients had Stage IIIC endometrial cancer with direct extension of the primary tumor. The 5-year OS rate for all patients was 40% with NAT, 56% after EBRT, and 64% after EBRT/BT. Adjuvant RT improved survival compared with NAT (p <0.001). In patients with organ-confined Stage IIIC endometrial cancer, the 5-year OS rate was 50% for NAT, 64% for EBRT, and 67% for EBRT/BT. Again, adjuvant RT contributed to improved survival compared with NAT (p = 0.02). In patients with Stage IIIC endometrial cancer and direct tumor extension, the 5-year OS rate was 34% for NAT, 47% for EBRT, and 63% for EBRT/BT. RT improved OS compared with NAT (p <0.001). Also, in this high-risk subgroup, adding BT to EBRT was superior to EBRT alone (p = 0.002). CONCLUSION: Women with Stage IIIC endometrial cancer receiving adjuvant EBRT and EBRT/BT had improved OS compared with patients receiving NAT. When direct extension of the primary tumor was present, the addition of BT to EBRT was even more beneficial.     

Stage II adenocarcinoma of the endometrium: adjuvant radiotherapy and recurrence patterns

PURPOSE: Review patterns of recurrence for Stage II endometrial cancer in a community practice. METHODS AND MATERIALS: A retrospective review of patients with endometrial cancer diagnosed between 1985-2002. Patients were excluded for Stages I, III, or IV or treatment with preoperative pelvic radiation (external beam radiation therapy [EBRT]). RESULTS: Eighty-six patients with a mean follow-up of 70 months are reported. Higher risk patients were selected for adjuvant radiation with no apparent differences for those receiving only EBRT compared with EBRT with brachytherapy. Five-year actuarial vaginal, pelvic sidewall/nodal, and metastatic control rates were 100% and 100%, 96.9% and 100%, and 79% and 84.2% for patients receiving EBRT or EBRT with brachytherapy. Overall survival rates were 70.5% and 75.8%, and cause-specific survival rates were 78.8% and 82.9% for those receiving EBRT or EBRT with brachytherapy. A select group was observed and experienced one vaginal recurrence with overall and cause-specific survival rates of 100%. CONCLUSION: In higher risk patients with Stage II, adjuvant EBRT achieves excellent vaginal and pelvic sidewall/nodal control without apparent benefit from additional brachytherapy. Select patients may not require adjuvant treatment.     

Clinical evaluation of proton radiotherapy for non-small-cell lung cancer

PURPOSE: To evaluate the clinical results of proton radiotherapy for patients with non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Between 1983 and 2000, 51 NSCLC patients were treated with proton beams at the University of Tsukuba. There were 28 patients in Stage I, 9 in Stage II, 8 in Stage III, 1 in Stage IV, and 5 with recurrent disease. Thirty-three patients had squamous cell carcinoma, 17 had adenocarcinoma, and 1 had large-cell carcinoma. Median fraction and total doses given were 3.0 Gy (range 2.0-6.0 Gy), and 76.0 Gy (range 49.0-93.0 Gy), respectively. RESULTS: The 5-year overall survival rate was 29% for all patients, 70% for 9 Stage IA patients, and 16% for 19 Stage IB patients, respectively (IA vs. IB: p < 0.05). The 5-year in-field local control rate was higher in patients with Stage IA (89%) when compared with those with Stage IB (39%). Forty-seven patients (92%) experienced acute lung toxicity of Grade 1 or less; 3 had Grade 2, 1 had Grade 3, and none experienced Grade 4 or higher. Patients in the present series showed very little late toxicity. CONCLUSIONS: Proton therapy is a very safe and effective treatment for patients with NSCLC, especially for those with early stages. The relative merit of proton therapy in comparison with stereotactic photon radiotherapy or three-dimensional conformal photon radiotherapy remains to be defined through future clinical trials.     

Dosimetric correlations of acute esophagitis in lung cancer patients treated with radiotherapy

PURPOSE: To evaluate the factors associated with acute esophagitis in lung cancer patients treated with thoracic radiotherapy. METHODS AND MATERIALS: We examined 35 patients with non-small-cell lung cancer (n = 27, 77%) and small-cell lung cancer (n = 8, 23%) treated with thoracic radiotherapy between February 2003 and November 2004. The median patient age was 70 years (range, 50-83 years). The disease stage was Stage I in 2 patients (6%), Stage II in 1 (3%), Stage IIIa in 10 (28%), Stage IIIb in 9 (26%), and Stage IV in 9 (26%); 4 patients (11%) had recurrent disease after surgery. A median dose of 60 Gy (range, 50-67 Gy) was given to the isocenter and delivered in single daily fractions of 1.8 or 2 Gy. With heterogeneity corrections, the median given dose to the isocenter was 60.3 Gy (range, 49.9-67.2 Gy). Of the 35 patients, 30 (86%) received concurrent chemotherapy consisting of a platinum agent, cisplatin or carboplatin, combined with paclitaxel in 18 patients (52%), irinotecan hydrochloride in 7 (20%), vincristine sulfate and etoposide in 2 (5%), vinorelbine ditartrate in 1 (3%), etoposide in 1 (3%), and docetaxel in 1 patient (3%). Three of these patients underwent induction therapy with cisplatin and irinotecan hydrochloride, administered before thoracic radiotherapy, and concurrent chemotherapy. Esophageal toxicity was graded according to the Radiation Therapy Oncology Group criteria. The following factors were analyzed with respect to their association with Grade 1 or worse esophagitis by univariate and multivariate analyses: age, gender, concurrent chemotherapy, chemotherapeutic agents, maximal esophageal dose, mean esophageal dose, and percentage of esophageal volume receiving >10 to >65 Gy in 5-Gy increments. RESULTS: Of the 35 patients, 25 (71%) developed acute esophagitis, with Grade 1 in 20 (57%) and Grade 2 in 5 (14%). None of the patients had Grade 3 or worse toxicity. The most significant correlation was between esophagitis and percentage of esophageal volume receiving >35 Gy on univariate (p = 0.002) and multivariate (p = 0.018) analyses. CONCLUSION: The percentage of esophageal volume receiving >35 Gy was the most statistically significant factor associated with mild acute esophagitis.     

Use of individual fraction size data from 3756 patients to directly determine the alpha/beta ratio of prostate cancer

PURPOSE: To examine the effect of fraction size and total dose of radiation on recurrence of localized prostate cancer. METHODS AND MATERIALS: A total of 3756 patients treated with radiation monotherapy at three institutions were analyzed, including 185 high-dose-rate brachytherapy (HDRB) boost patients. The 5th to 95th centiles of external beam radiotherapy (EBRT) fraction sizes and doses were 1.8 to 2.86 Gy, and 57.4 to 77.4 Gy, respectively, and HDRB fractional doses were between 5.5 and 12 Gy, totaling 147 unique fractionation schedules. Failure was defined by one biochemical (nadir + 2 ng/ml) and two advanced disease endpoints. The alpha/beta ratios were estimated via a proportional hazards model stratified by risk severity and institution. RESULTS: The alpha/beta ratio using biochemical recurrence was 3.7 Gy (95% confidence interval [95% CI], 1.1, infinity Gy) for EBRT-only cases and 2.6 Gy (95% CI, 0.9, 4.8 Gy) after the addition of HDRB data. This estimate was highly dependent on an HDRB homogeneity correction factor (120% HDRB dose increase; alpha/beta ratio 4.5 Gy, 95% CI 1.6, 8.7 Gy). A 5-Gy increase in total dose reduced the hazard of failure by 16% (95% CI 11, 21%, p < 0.0001), and had more impact as follow-up matured (p < 0.0003). The clinically advanced endpoints concurred with the biochemical failure results, albeit with less precision. CONCLUSIONS: This study supports the concept that the alpha/beta ratio of prostate cancer is low, although considerable uncertainty remains in the estimated value. Outcome data from EBRT studies using substantially higher doses per fraction are needed to show increased precision in these estimates.     

Ic期子宫内膜癌患者中MPA和EBRT的联合疗效

Objective: To report the comparative effect of combined medroxyprogesterone acetate (MPA) and external beam pelvic radiotherapy (EBRT) with EBRT alone on local or distant recurrences, overall survival and treatment related toxicities in patients with stage Ic grade 3 endometrial cancer. Methods: A retrospective review of 80 International Federation of Gyne-cology and Obstetrics (FIGO) stage Ic grade 3 endometrial carcinoma patients treated between October 1994 and October 2004 at Renmin Hospital, Wuhan University, China was performed. All patients underwent surgery, of which 40 patients in arm I received combined MPA and EBRT while in arm II 40 patients received only adjuvant EBRT after surgery. The median dose of EBRT in arm I was 50 Gy (range 36-54 Gy) and in arm II was 45.2 Gy (range 43.2-50.4 Gy). Multivariate analysis was performed for the prognostic factors and Kaplan-Meier method was used for overall survival. Results: Of the 80 eligible patients, 40 in each group could be evaluated. The follow-up times ranged from 4-98 months with a median of 45 months. The overall survival rates at five years were 73% among patients treated with combined MPA and EBRT and 28.2% among patients treated with EBRT alone (P < 0.001). The rate of distant metastasis was significantly higher among patients treated with EBRT alone group than combined MPA and EBRT (55% vs 25%, P = 0.006) while no difference in loco regional recur-rence rates was observed in both treatment groups. Most of the side effects observed in the combined MPA and EBRT group. Age (P < 0.001) and the presence of progesterone receptors (P = 0.003) were independent significant prognostic factors for overall survival in multiple regression analysis. Conclusion: We has been concluded that the addition of progestagen to external beam pelvic radiotherapy significantly improved survival and reduced distant metastasis among women with stage Ic grade 3 endometrial cancer.     

Definitive radiation therapy for squamous cell carcinoma of the vagina

PURPOSE: To evaluate outcome and describe clinical treatment guidelines for patients with primary squamous cell carcinoma of the vagina treated with definitive radiation therapy. METHODS AND MATERIALS: Between 1970 and 2000, a total of 193 patients were treated with definitive radiation therapy for squamous cell carcinoma of the vagina at The University of Texas M. D. Anderson Cancer Center. The patients' medical records were reviewed to obtain information about patient, tumor, and treatment characteristics, as well as outcome and patterns of recurrence. Surviving patients were followed for a median of 137 months. Survival rates were calculated using the Kaplan-Meier method, with differences assessed using log-rank tests. RESULTS: Disease-specific survival (DSS) and pelvic disease control rates correlated with International Federation of Gynecology and Obstetrics (FIGO) stage and tumor size. At 5 years, DSS rates were 85% for the 50 patients with Stage I, 78% for the 97 patients with Stage II, and 58% for the 46 patients with Stage III-IVA disease (p = 0.0013). Five-year DSS rates were 82% and 60% for patients with tumors < or =4 cm or >4 cm, respectively (p = 0.0001). At 5 years, pelvic disease control rates were 86% for Stage I, 84% for Stage II, and 71% for Stage III-IVA (p = 0.027). The predominant mode of relapse after definitive radiation therapy was local-regional (68% and 83%, respectively, for patients with stages I-II or III-IVA disease). The incidence of major complications was correlated with FIGO stage; at 5 years, the rates of major complications were 4% for Stage I, 9% for Stage II, and 21% for Stage III-IVA (p < 0.01). CONCLUSIONS: Excellent outcomes can be achieved with definitive radiation therapy for invasive squamous cell carcinoma of the vagina. However, to achieve these results, treatment must be individualized according to the site and size of the tumor at presentation and the response to initial external-beam radiation therapy. Brachytherapy plays an important role in the treatment of many vaginal cancers but should be carefully selected and applied to obtain optimal coverage of the target volume.     

Stereotactic body radiotherapy as boost for organ-confined prostate cancer

Stereotactic body radiotherapy (SBRT) boost following external beam radiation therapy (EBRT) for advanced localized prostate cancer may reduce toxicity while escalating the dose. We present preliminary biochemical control and urinary, rectal and sexual toxicities for 73 patients treated with SBRT as a boost to EBRT. Forty-one intermediate- and 32 high-risk localized prostate cancer patients received 45 Gy EBRT with SBRT boost. Twenty-eight patients (38.3%) received a total SBRT boost dose of 18 Gy (3 fractions of 6 Gy), 28 patients (38.3%) received 19.5 Gy (3 fractions of 6.5 Gy), and 17 patients (23.2%) received 21 Gy (3 fractions of 7 Gy). Toxicity was assessed using the Radiation Therapy Oncology Group urinary and rectal toxicity scale. Biochemical failure was assessed using the Phoenix definition. The median follow-up was 33 months (range, 22 - 43 months). Less than 7% Grade II and no higher grade acute toxicities occurred. To date, one Grade III and no Grade IV late toxicities occurred. For the 97% of patients with 24 months minimum follow-up, 71.8% achieved a PSA nadir threshold of 0.5 ng/mL. Three intermediate-risk and seven high-risk biochemical failures occurred; one high-risk patient died of his cancer. Three-year actuarial biochemical control rates were 89.5% and 77.7% for intermediate- and high-risk patients, respectively. SBRT boost for prostate cancer treatment is safe and feasible with minimal acute toxicity. At 33 months late toxicity and biochemical control are promising. Long-term durability of these findings remains to be established.     

Combination external beam radiotherapy and high-dose-rate intracavitary brachytherapy for uterine cervical cancer: analysis of dose and fractionation schedule

PURPOSE: To determine an appropriate dose and fractionation schedule for a combination of external beam radiotherapy (EBRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT) for uterine cervical cancer. METHODS: Eighty-eight patients with uterine cervical squamous cell carcinoma treated with EBRT and HDR-ICBT were analyzed. Twenty-five patients were classified as early disease (nonbulky Stage I/II, less than 4-cm diameter) and 63 patients as advanced disease (greater than 4 cm diameter or Stage IIIB) according to the American Brachytherapy Society definition. Tumor diameter was measured by MRI. Pelvic EBRT was delivered before applications of ICBT. HDR-ICBT was performed once a week, with a fraction point A dose of 6 Gy. Source loadings corresponded to the Manchester System for uterine cervical cancer. No planned optimization was done. A Henschke-type applicator was mostly used (86%). Median cumulative biologic effective dose (BED) at point A (EBRT + ICBT) was 64.8 Gy(10) (range: 48-76.8 Gy(10)) for early disease, and 76.8 Gy(10) (range: 38.4-86.4 Gy(10)) for advanced disease. Median cumulative BED at ICRU 38 reference points (EBRT + ICBT) was 97.7 Gy(3) (range: 59.1-134.4 Gy(3)) at the rectum, 97.8 Gy(3) (range: 54.6-130.4 Gy(3)) at the bladder, and 324 Gy(3) (range: 185.5-618 Gy(3)) at the vagina. Actuarial pelvic control rate and late complication rate were analyzed according to cumulative dose and calculated BED. RESULTS: The 3-year actuarial pelvic control rate was 82% for all 88 patients: 96% for those with early disease, and 76% for advanced disease. For pelvic control, no significant dose-response relationship was observed by treatment schedules and cumulative BED at point A for both early and advanced disease. The 3-year actuarial late complication rates (Grade > or =1) were 12% for proctitis, 11% for cystitis, and 14% for enterocolitis. There were significant differences on the incidence of proctitis (p < 0.0001) and enterocolitis (p < 0.0001), but not for cystitis by the treatment schedules and cumulative point A BED. All 4 patients treated with 86.4 Gy(10) at point A suffered both proctitis and enterocolitis. Patients with cumulative BED at rectal point of > or =100 Gy(3) had significantly higher incidence of proctitis (31% vs. 4%, p = 0.013). CONCLUSIONS: In view of the therapeutic ratio, cumulative BED 70-80 Gy(10) at point A is appropriate for uterine cervical cancer patients treated with a combination of EBRT and HDR-ICBT. Present results and data from other literatures suggested that cumulative BED at the rectal point should be kept below 100-120 Gy(3) to prevent late rectal complication.     

Modeling normal tissue complication probability from repetitive computed tomography scans during fractionated high-dose-rate brachytherapy and external beam radiotherapy of the uterine cervix

PURPOSE: To calculate the normal tissue complication probability (NTCP) of late radiation effects on the rectum and bladder from repetitive CT scans during fractionated high-dose-rate brachytherapy (HDRB) and external beam radiotherapy (EBRT) of the uterine cervix and compare the NTCP with the clinical frequency of late effects. METHODS AND MATERIALS: Fourteen patients with cancer of the uterine cervix (Stage IIb-IVa) underwent 3-6 (mean, 4.9) CT scans in treatment position during their course of HDRB using a ring applicator with an Iridium stepping source. The rectal and bladder walls were delineated on the treatment-planning system, such that a constant wall volume independent of organ filling was achieved. Dose-volume histograms (DVH) of the rectal and bladder walls were acquired. A method of summing multiple DVHs accounting for variable dose per fraction were applied to the DVHs of HDRB and EBRT together with the Lyman-Kutcher NTCP model fitted to clinical dose-volume tolerance data from recent studies. RESULTS: The D(mean) of the DVH from EBRT was close to the D(max) for both the rectum and bladder, confirming that the DVH from EBRT corresponded with homogeneous whole-organ irradiation. The NTCP of the rectum was 19.7% (13.5%, 25. 9%) (mean and 95% confidence interval), whereas the clinical frequency of late rectal sequelae (Grade 3-4, RTOG/EORTC) was 13% based on material from 200 patients. For the bladder the NTCP was 61. 9% (46.8%, 76.9%) as compared to the clinical frequency of Grade 3-4 late effects of 14%. If only 1 CT scan from HDRB was assumed available, the relative uncertainty (standard deviation or SD) of the NTCP value for an arbitrary patient was 20-30%, whereas 4 CT scans provided an uncertainty of 12-13%. CONCLUSION: The NTCP for the rectum was almost consistent with the clinical frequency of late effects, whereas the NTCP for bladder was too high. To obtain reliable (SD of 12-13%) NTCP values, 3-4 CT scans are needed during 5-7 fractions of HDRB treatments.     

Predictors of severe gastrointestinal toxicity after external beam radiotherapy and interstitial brachytherapy for advanced or recurrent gynecologic malignancies

PURPOSE: The aim of this retrospective review of patients with gynecologic malignancies treated with external beam radiotherapy (EBRT) and interstitial brachytherapy was to determine the rate of Grade > or =2 rectovaginal fistula and Grade > or =4 small bowel obstruction as defined by the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0. METHODS AND MATERIALS: Thirty-six patients with primary and recurrent gynecologic cancers were treated with EBRT and interstitial brachytherapy. Median doses to tumor, bladder, and rectum were 75 Gy, 61 Gy, and 61 Gy, respectively. A univariate analysis was performed to identify variables that correlated with toxicity. RESULTS: At median follow-up of 19 months, the 3-year risk of small bowel obstruction was 6%. Those patients with prior abdomino-pelvic surgery who received EBRT with antero-posterior fields had higher rates of obstruction than patients without prior abdomino-pelvic surgery or those who received EBRT with four fields (50% vs. 0%, p < 0.0001). The 3-year risk of rectovaginal fistula was 18% and was significantly higher in patients who received >76 Gy to the rectum compared with those who received < or =76 Gy (100% vs. 7%, p = 0.009). CONCLUSIONS: Patients treated with EBRT and interstitial brachytherapy after abdomino-pelvic surgery should receive EBRT with four fields and the cumulative rectal dose should be < or =76 Gy.     

Radical hysterectomy for stage I and II endometrial carcinoma: a retrospective analysis of 179 cases

Total hysterectomy with bilateral salpingo oophorectomy is the traditional treatment for endometrial carcinoma. In an effort to improve local control rates, we have surgically treated our Stage I and II patients with radical hysterectomy and pelvic lymphadenectomy (RH-PL). Between 1976 and 1987 we have treated 179 patients with endometrial adenocarcinoma (125 Stage I and 54 Stage II) with the following modalities. Uterovaginal brachytherapy (60 Gy) was performed first and then 6 weeks later an RH-PL was performed. Twenty-nine patients received external pelvic irradiation (45 Gy) because of tumor invasion beyond the internal two-thirds of the myometrium and/or lymph node involvement. The local control rate was 87% (92% for Stage I, 76% for Stage II). Distant metastases occurred in 24 patients (13%). Five-year actuarial survival rates were 80% for Stage I and 61% for Stage II patients. Prognostic factors were nodal status, histological grading, depth of tumor myometrial invasion, histologic status of the hysterectomy specimen, and peritoneal cytology. Late severe complications occurred for 13 patients (7%). These results are comparable to those published for patients treated with less extensive surgery. We conclude that such an extensive surgery (especially pelvic lymphadenectomy) appears to be useless for all patients with bad prognostic factors requiring pelvic external irradiation. We only still perform external iliac node samples for patients with Stage I grade 1 tumors without deep tumor invasion into the myometrium.     

Two fractions of high-dose-rate brachytherapy in the management of cervix cancer: clinical experience with and without chemotherapy

PURPOSE: In recent years, high-dose-rate brachytherapy has become popular in the management of carcinoma of the uterine cervix, because it eliminates many of the problems associated with low-dose-rate brachytherapy. However, the optimum time-dose-fractionation remains controversial. Two fractions of high-dose-rate brachytherapy are convenient for patients, but most radiation oncologists in the United States do not use them, because of fear that they could lead to excessive rectal or bladder toxicity. Here we present our experience, which suggests that a two-fraction regimen is indeed safe and effective. METHODS: We treated 49 patients with Stages I-III biopsy-proven carcinoma of the uterine cervix by external beam radiation therapy (EBRT), plus two fractions of high-dose-rate brachytherapy. The histology was squamous cell carcinoma in 43 patients (88%) and nonsquamous in 6 (12%). The median size of the primary tumor was 6 cm (range: 3-10 cm). Each patient received EBRT to the pelvis to a median dose of 45 Gy (range: 41.4-50.4 Gy), followed by a parametrial boost when indicated. Thirty patients (61%) also received irradiation to the para-aortic lymph nodes to a dose of 45 Gy. After EBRT, each patient underwent two applications of high-dose-rate brachytherapy, 1 week apart. The dose delivered to point A was 9 Gy per application for 49 applications (50%) and 9.4 Gy for 43 applications (44%), and it varied from 7 to 11 Gy for the rest (6%). The total dose to the rectum from both high-dose-rate brachytherapy applications ranged from 4.7 to 11.7 Gy (median: 7.1 Gy), and the total dose to the bladder from 3.8 to 15.5 Gy (median: 10.5 Gy). Twenty-five of the 49 patients (51%) received concomitant chemotherapy (cisplatin 20 mg/m(2)/day for 5 days) during the first and fourth weeks of EBRT and once after the second high-dose-rate brachytherapy application. Chemotherapy was not assigned in a randomized fashion. The use of chemotherapy increased during the time period spanned by this study as increasing evidence supporting the use of chemotherapy began to appear. RESULTS: The observed survival rates after 2, 3, and 5 years were 83%, 78%, and 78%, respectively. The surviving patients have been followed up for a median of 3 years (range: 2-6 years). Eight of the 49 patients suffered local failures. Among patients treated without chemotherapy, the 3-year local control rate was 77%; it was 88% among those receiving chemotherapy. There have been no regional failures. Four patients developed distant metastases. At 3 years, 91% of the patients in each group were free of distant metastases. Ten of the 49 patients (20%) suffered Grade 3 acute toxicity; 11 (22%) had Grade 4. Among the 24 patients treated without chemotherapy, only 1 (4%) suffered Grade 3 toxicity. Among the 25 patients receiving chemotherapy, in contrast, 8 (32%) suffered Grade 3 and 12 (48%) Grade 4 acute toxicity. Only 2 patients suffered late toxicity: One suffered Grade 2 and the other Grade 3 late toxicity. The actuarial risk of Grade 2 or worse late toxicity was 5%, with or without chemotherapy. CONCLUSIONS: Our experience suggests that two fractions of high-dose-rate brachytherapy are safe and effective in the management of cervix cancer, even in conjunction with concomitant cisplatin. The fears that the use of two fractions would lead to excessive rectal or bladder toxicity proved unfounded. Guidelines for ensuring a low complication rate are discussed.